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Pre-Clinical Studies

Mesenchymal stem cells are susceptible to human herpesviruses, but viral DNA cannot be detected in the healthy seropositive individual

Bone Marrow Transplantation volume 37, pages 1051–1059 (2006)Cite this article

Abstract

Allogeneic stem cell transplantation is often complicated by reactivation of herpesviruses. Mesenchymal stem cells (MSC) are immunomodulatory and may be used to treat graft-versus-host disease. We investigated if herpesviruses infect and can be transmitted by MSC, and if MSC suppress immune responses to various infectious agents. Mesenchymal stem cells from healthy seropositive donors were evaluated with polymerase chain reaction for the most common herpesviruses: cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, Epstein–Barr virus (EBV) and varicella zoster virus. The cytopathological effect (CPE) was investigated and viral antigens analyzed by immunofluorescence after in vitro exposure to CMV, HSV-1 and EBV. We also studied MSC effect on lymphocyte stimulation induced by various infectious agents. No viral DNA could be detected in MSC isolated from healthy seropositive individuals. However, a CPE was noted and intracellular viral antigens detected after infection in vitro by CMV and HSV-1, but not by EBV. The CMV and HSV-1 infections were productive. Lymphocyte proliferation by herpesviruses, candida mannan and protein A from Staphylococcus aureus was suppressed by MSC. The data indicate that the risk of herpesvirus transmission by transplantation of MSC from healthy seropositive donors is low. However, MSC may be susceptible to infection if infused in a patient with CMV or HSV-1 viremia. MSC transplantation may compromise the host's defense against infectious agents.

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Acknowledgements

This study was supported by grants from the Swedish Cancer Society (4562-B03-XAC), the Children's Cancer Foundation (03/007), the Swedish Research Council (K2003-32XD-14716-01A), the Stockholm Cancer Society, the Swedish Society of Medicine and the Karolinska Institutet.

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Authors and Affiliations

  1. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    M Sundin, I Rasmusson, B Sundberg, O Ringdén & K Le Blanc

  2. Divison of Clinical Virology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    C Örvell

  3. Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden

    O Ringdén & K Le Blanc

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  1. M Sundin
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Correspondence to M Sundin.

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Sundin, M., Örvell, C., Rasmusson, I. et al. Mesenchymal stem cells are susceptible to human herpesviruses, but viral DNA cannot be detected in the healthy seropositive individual. Bone Marrow Transplant 37, 1051–1059 (2006). https://doi.org/10.1038/sj.bmt.1705368

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